tbuckley/cabot-search huggingface dataset:
Fluvoxamine vs Placebo and Time to Recovery in Outpatients With Mild to Moderate COVID-19
Authors: Sahar Ashraf, Nauman Ashraf
Journal: JAMA (2023)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
RGS2-mediated translational control mediates cancer cell dormancy and tumor relapse
Authors: Jaebeom Cho, Hye-Young Min, Ho Jin Lee, Seung Yeob Hyun, Jeong Yeon Sim, Myungkyung Noh, Su Jung Hwang, Shin-Hyung Park, Hye-Jin Boo, Hyo-Jong Lee, Sungyoul Hong, Rang-Woon Park, Young Kee Shin, Mien-Chie Hung, Ho-Young Lee
Journal: Journal of Clinical Investigation (2023)
Integrative Single-Cell and Bulk Transcriptomes Analyses Identify Intrinsic HNSCC Subtypes with Distinct Prognoses and Therapeutic Vulnerabilities
Authors: Yibin Dai, Ziyu Wang, Yingchao Xia, Jin Li, Yaping Wu, Yanling Wang, Hongbing Jiang, Jie Cheng
Journal: Clinical Cancer Research (2023)

Tumor heterogeneity in head and neck squamous cell carcinoma (HNSCC) profoundly compromises patient stratification, personalized treatment planning, and prognostic prediction, which underscores the urgent need for more effective molecular subtyping for this malignancy. Here, we sought to define the intrinsic epithelial subtypes for HNSCC by integrative analyses of single-cell and bulk RNA sequencing datasets from multiple cohorts and assess their molecular features and clinical significance.Malignant epithelial cells were identified from single-cell RNA sequencing (scRNA-seq) datasets and subtyped on the basis of differentially expressed genes. Subtype-specific genomic/epigenetic abnormalities, molecular signaling, genetic regulatory network, immune landscape, and patient survival were characterized. Therapeutic vulnerabilities were further predicted on the basis of drug sensitivity datasets from cell lines, patient-derived xenograft models, and real-world clinical outcomes. Novel signatures for prognostication and therapeutic prediction were developed by machine learning and independently validated.Three intrinsic consensus molecular subtypes (iCMS1-3) for HNSCC were proposed from scRNA-seq analyses and recapitulated in 1,325 patients from independent cohorts using bulk-sequencing datasets. iCMS1 was characterized by EGFR amplification/activation, stromal-enriched environment, epithelial-to-mesenchymal transition, worst survival, and sensitivities to EGFR inhibitor. iCMS2 was featured by human papillomavirus-positive oropharyngeal predilection, immune-hot, susceptibilities to anti-PD-1, and best prognosis. Moreover, iCMS3 displayed immune-desert and sensitivities to 5-FU and MEK, STAT3 inhibitors. Three novel, robust signatures derived from iCMS subtype-specific transcriptomics features were developed by machine learning for patient prognostication and cetuximab and anti-PD-1 response predictions.These findings reiterate molecular heterogeneity of HNSCC and advantages of scRNA-seq in pinpointing cellular diversities in complex cancer ecosystems. Our HNSCC iCMS regime might facilitate accurate patient stratification and individualized precise treatment.
Core indicators related to the elimination of hepatitis B and C virus infection in South Korea: A nationwide study
Authors: Chang Hun Lee, Gwang Hyeon Choi, Hwa Young Choi, Sojung Han, Eun Sun Jang, Young Eun Chon, Young Chang, Kyung-Ah Kim, Do Young Kim, Hyung Joon Yim, Hye-Lin Kim, Sook-Hyang Jeong, In Hee Kim
Journal: Clinical and Molecular Hepatology (2023)

Background/Aims: To eliminate hepatitis B virus (HBV) and hepatitis C virus (HCV) according to the World Health Organization (WHO) criteria in 2021, this study investigated the national core indicators representing the current status of viral hepatitis B and C in South Korea.Methods: We analyzed the incidence, linkage-to-care, treatment, and mortality rates of HBV and HCV infection using the integrated nationwide big data of South Korea.Results: According to data from 2018–2020, the incidence of acute HBV infection in South Korea was 0.71 cases per 100,000 population; tthe linkage-to-care rate was only 39.4%. Among those who need hepatitis B treatment, the treatment rate was 67.3%, which was less than 80% reported in the WHO program index. The annual liver-related mortality due to HBV was 18.85 cases per 100,000 population, exceeding the WHO target of four; the most frequent cause of death was liver cancer (54.1%). The annual incidence of newly diagnosed HCV infection was 11.9 cases per 100,000 population, which was higher than the WHO impact target of five. Among HCV-infected patients, the linkage-to-care rate was 65.5% while the treatment rate was 56.8%, which were below the targets of 90% and 80%, respectively. The liver-related annual mortality rate due to HCV infection was 2.02 cases per 100,000 population.Conclusions: Many of the current indicators identified in the Korean population did not satisfy the WHO criteria for validation of viral hepatitis elimination. Hence, a comprehensive national strategy should be urgently developed with continuous monitoring of the targets in South Korea.
Partial tumor irradiation plus pembrolizumab in treating large advanced solid tumor metastases
Authors: Mark C. Korpics, Benjamin E. Onderdonk, Rebekah E. Dadey, Jared H. Hara, Lilit Karapetyan, Yuanyuan Zha, Theodore G. Karrison, Adam C. Olson, Gini F. Fleming, Ralph R. Weichselbaum, Riyue Bao, Steven J. Chmura, Jason J. Luke
Journal: Journal of Clinical Investigation (2023)

BACKGROUND. We previously demonstrated the safety of stereotactic body radiotherapy followed by pembrolizumab (SBRT+P) in patients with advanced solid tumors. This phase I clinical trial was expanded to study the safety of partial tumor irradiation (partial-Rx). We assessed irradiated local failure (LF) and clinical outcomes with correlations to biomarkers including CD8+ T cell radiomics score (RS) and circulating cytokines.
Conditional survival in multiple myeloma and impact of prognostic factors over time
Authors: Nadine H. Abdallah, Alexandra N. Smith, Susan Geyer, Moritz Binder, Patricia T. Greipp, Prashant Kapoor, Angela Dispenzieri, Morie A. Gertz, Linda B. Baughn, Martha Q. Lacy, Suzanne R. Hayman, Francis K. Buadi, David Dingli, Yi L. Hwa, Yi Lin, Taxiarchis Kourelis, Rahma Warsame, Robert A. Kyle, S. Vincent Rajkumar, Shaji K. Kumar
Journal: Blood Cancer Journal (2023)

Overall survival estimates from diagnosis are valuable for guiding treatment, but do not consider the years already survived. Conditional survival (CS) provides dynamic survival predictions over time. This study was conducted to estimate CS at 1-8 years from diagnosis and the impact of baseline prognostic factors on CS in multiple myeloma (MM) patients. This is a retrospective study including 2556 MM patients diagnosed between 2004 and 2019. CS (t | s) was defined as the probability of surviving t years given survival of s years. Median age was 64 years. Median follow-up was 6.2 years and median overall survival from diagnosis was 7.5 years. The 5-year CS estimates at s = 0, 1, 2, 3, and 5 years were 0.64, 0.61, 0.61, 0.61, and 0.58, respectively. On multivariate analysis, age ≥ 65 and proteasome inhibitor+immunomodulatory-based induction were associated with decreased survival and increased survival, respectively, retained at 5 years. The adverse impact of 1q gain/amplification, high-risk IgH translocation, and ISS-3 was significant at 1 and 3 years but not 5 years. Chromosome 17 abnormality was associated with decreased survival only at 1 year. Among MM patients, 5-year CS was stable at 1-5 years from diagnosis. The prognostic impact of high-risk cytogenetic factors decreased with additional years survived.
Paving a way to treat spastic paraplegia 50
Authors: Jonathan R. Brent, Han-Xiang Deng
Journal: Journal of Clinical Investigation (2023)

Spastic paraplegia 50 (SPG50) is a rare neurodegenerative disease caused by loss-of-function mutations in AP4M1. There are no effective treatments for SPG50 or any other type of SPG, and current treatments are limited to symptomatic management. In this issue of the JCI, Chen et al. provide promising data from preclinical studies that evaluated the efficacy and safety profiles of an AAV-mediated AP4M1 gene replacement therapy for SPG50. AAV/AP4M1 gene replacement partly rescued functional defects in SPG50 cellular and mouse models, with acceptable safety profiles in rodents and monkeys. This work represents a substantial advancement in therapeutic development of SPG50 treatments, establishing the criteria for taking AAV9/AP4M1 gene therapy to clinical trials.
2-Year Outcomes Following Transcatheter Tricuspid Valve Replacement Using the EVOQUE System
Authors: Lukas Stolz, Ludwig T. Weckbach, Rebecca T. Hahn, Andrew G. Chatfield, Neil P. Fam, Ralph Stephan von Bardeleben, Charles J. Davidson, Paul A. Grayburn, Firas Zahr, Jörg Hausleiter
Journal: Journal of the American College of Cardiology (2023)
Artificial intelligence-driven radiomics study in cancer: the role of feature engineering and modeling
Authors: Yuan-Peng Zhang, Xin-Yun Zhang, Yu-Ting Cheng, Bing Li, Xin-Zhi Teng, Jiang Zhang, Saikit Lam, Ta Zhou, Zong-Rui Ma, Jia-Bao Sheng, Victor C. W. Tam, Shara W. Y. Lee, Hong Ge, Jing Cai
Journal: Military Medical Research (2023)

Modern medicine is reliant on various medical imaging technologies for non-invasively observing patients' anatomy. However, the interpretation of medical images can be highly subjective and dependent on the expertise of clinicians. Moreover, some potentially useful quantitative information in medical images, especially that which is not visible to the naked eye, is often ignored during clinical practice. In contrast, radiomics performs high-throughput feature extraction from medical images, which enables quantitative analysis of medical images and prediction of various clinical endpoints. Studies have reported that radiomics exhibits promising performance in diagnosis and predicting treatment responses and prognosis, demonstrating its potential to be a non-invasive auxiliary tool for personalized medicine. However, radiomics remains in a developmental phase as numerous technical challenges have yet to be solved, especially in feature engineering and statistical modeling. In this review, we introduce the current utility of radiomics by summarizing research on its application in the diagnosis, prognosis, and prediction of treatment responses in patients with cancer. We focus on machine learning approaches, for feature extraction and selection during feature engineering and for imbalanced datasets and multi-modality fusion during statistical modeling. Furthermore, we introduce the stability, reproducibility, and interpretability of features, and the generalizability and interpretability of models. Finally, we offer possible solutions to current challenges in radiomics research.
Back to the future: evolutionary biology reveals a key regulatory switch in neuroblastoma pathogenesis
Authors: Jaime N. Wertman, Jason N. Berman
Journal: Journal of Clinical Investigation (2023)

While MYCN expression is an important contributing factor to heterogeneity in the natural history of neuroblastoma (NBL), a mechanistic understanding of this often mutationally quiet tumor has remained elusive. In this issue of the JCI, Weichert-Leahey and authors focused on the adrenergic and mesenchymal core regulatory circuitries (CRC) as NBL transcriptional programs. The authors previously showed that overexpression of LIM-domain-only 1 (LMO1), a transcriptional coregulator, synergizes with MYCN to accelerate tumor formation and metastasis in an NBL-zebrafish model. They now demonstrate experimentally, using genome-edited zebrafish, that a polymorphism in the human rs2168101 locus of the LMO1 gene determines which CRC is active in a tumor. In some cases, LMO3 compensated for LMO1 loss and drove the adrenergic CRC in MYCN-positive NBL. This study exemplifies the value of evolutionary relationships and zebrafish models in the investigation of human disease and reveals pathways of NBL development that may affect prevention or intervention strategies.
Another tool against cytomegalovirus after allogeneic hematopoietic cell transplantation
Authors: George L. Chen, Elizabeth J. Shpall
Journal: Journal of Clinical Investigation (2023)

Cytomegalovirus (CMV) viremia from reactivation of latent infection is a common complication after allogeneic hematopoietic cell transplantation (HCT). Untreated, CMV viremia can progress to affect other organs, resulting in organ dysfunction with high morbidity and mortality. In this issue of the JCI, Prockop and authors demonstrate that third-party donor T cells sensitized ex vivo to CMV pp65-derived overlapping pentadecapeptides are safe and effective for the treatment of CMV reactivation or CMV disease refractory to first-line pharmacotherapies occurring after HCT. They also provide insight into the biological differences between responders and nonresponders. This work confirms the utility of third-party CMV pp65 VSTs and suggests strategies for further improving the efficacy of this cell-therapy approach.
Sensitivity and specificity in affective and social learning in adolescence
Authors: Emily Towner, Gabriele Chierchia, Sarah-Jayne Blakemore
Journal: Trends in Cognitive Sciences (2023)

Adolescence is a period of heightened affective and social sensitivity. In this review we address how this increased sensitivity influences associative learning. Based on recent evidence from human and rodent studies, as well as advances in computational biology, we suggest that, compared to other age groups, adolescents show features of heightened Pavlovian learning but tend to perform worse than adults at instrumental learning. Because Pavlovian learning does not involve decision-making, whereas instrumental learning does, we propose that these developmental differences might be due to heightened sensitivity to rewards and threats in adolescence, coupled with a lower specificity of responding. We discuss the implications of these findings for adolescent mental health and education.
Epidemiology of Bladder Cancer in 2023: A Systematic Review of Risk Factors
Authors: Ibrahim Jubber, Sean Ong, Laura Bukavina, Peter C. Black, Eva Compérat, Ashish M. Kamat, Lambertus Kiemeney, Nathan Lawrentschuk, Seth P. Lerner, Joshua J. Meeks, Holger Moch, Andrea Necchi, Valeria Panebianco, Srikala S. Sridhar, Ariana Znaor, James W.F. Catto, Marcus G. Cumberbatch
Journal: European Urology (2023)

Bladder cancer (BC) is common worldwide and poses a significant public health challenge. External risk factors and the wider exposome (totality of exposure from external and internal factors) contribute significantly to the development of BC. Therefore, establishing a clear understanding of these risk factors is the key to prevention.
Rammya Mathew: Tackling overmedicalisation must become a political priority
Authors: Rammya Mathew
Journal: BMJ (2023)

Overmedicalisation has been around as a concept for more than 20 years, with campaigners ardently trying to shine a light on the harms of too much medicine. 1But you only have to speak to fellow colleagues to realise that it's still very much a peripheral concept.Most doctors still take the view that over-intervention is an infinitely better option than under-intervention.But from the extent of overmedicalisation I see in general practice alone, I don't believe that this is a helpful perspective.
Evaluation of a DoE based approach for comprehensive modelling of the effect of lipid nanoparticle composition on nucleic acid delivery
Authors: Yue Qin, Adam A. Walters, Nadia Rouatbi, Julie Tzu-Wen Wang, Hend Mohamed Abdel-Bar, Khuloud T. Al-Jamal
Journal: Biomaterials (2023)

Therapeutic nucleic acids (TNAs) comprise an alternative to conventional drugs for cancer therapy. Recently, stable nucleic acid lipid particles (SNALPs) have been explored to deliver TNA efficiently and safely both in vitro and in vivo. Small interfering RNA (siRNA) and messenger RNA (mRNA) based drugs have been suggested for a wide range of pathologies, and their respective lipid nanoparticle (LNP) formulations have been optimised using a Design of Experiments (DoE) approach. However, it is uncertain as to whether data obtained from DoE using simple experimental outputs can be used to generate a general heuristic for delivery of diverse TNA both in vitro and in vivo. Using plasmid DNA (pDNA), for which limited DoE optimisation has been performed, and siRNA to represent the two extremities of the TNA spectrum in terms of size and biological requirements, we performed a comparative DoE for both molecules and assessed the predictive qualities of the model both in vitro and in vivo. By producing a minimum run of 24 SNALP formulations with different lipid compositions incorporating either pDNA or siRNA, DoE models were successfully established for predicting the effect of individual lipid composition on particle size, TNA encapsulation and transfection both in vitro and in vivo. The results showed that the particle size, and in vitro and in vivo transfection efficiency of both pDNA and siRNA SNALP formulations were affected by lipid compositions. The encapsulation efficiency of pDNA SNALPs but not siRNA SNALPs was affected by the lipid composition. Notably, the optimal lipid compositions of SNALPs for pDNA/siRNA delivery were not identical. Furthermore, in vitro transfection efficiency could not be used to predict promising LNP candidates in vivo. The DoE approach described in this study may provide a method for comprehensive optimisation of LNPs for various applications. The model and optimal formulation described in this study can serve as a foundation from which to develop other novel NA containing LNPs for multiple applications such as NA based vaccines, cancer immunotherapies and other TNA therapies.
The association of obstructive sleep apnea with blood and cerebrospinal fluid biomarkers of Alzheimer’s dementia - A systematic review and meta-analysis
Authors: Brian Sheng Yep Yeo, Jin Hean Koh, Adele Chin Wei Ng, Shaun Loh, Anna See, Dennis Chuen Chai Seow, Song Tar Toh
Journal: Sleep Medicine Reviews (2023)
Safety, effectiveness, and cost-effectiveness of immediate versus delayed sequential bilateral cataract surgery in the Netherlands (BICAT-NL study): a multicentre, non-inferiority, randomised controlled trial
Authors: Lindsay Spekreijse, Rob Simons, Bjorn Winkens, Frank van den Biggelaar, Carmen Dirksen, Marjolijn Bartels, Ronald de Crom, Oege Goslings, Maurits Joosse, Jocelyn Kasanardjo, Peter Lansink, Theodorus Ponsioen, Nic Reus, Jan Schouten, Rudy Nuijts
Journal: The Lancet (2023)
BNT162b2 vaccine protection against omicron and effect of previous infection variant and vaccination sequence among children and adolescents in Singapore: a population-based cohort study
Authors: Chee Fu Yung, Deanette Pang, Kai Qian Kam, David C Lye, Benjamin Ong, Chia Yin Chong, Kelvin B Tan
Journal: The Lancet Child & Adolescent Health (2023)
Extracellular communication between brain cells through functional transfer of Cre mRNA mediated by extracellular vesicles
Authors: David Rufino-Ramos, Kevin Leandro, Pedro R.L. Perdigão, Killian O'Brien, Maria Manuel Pinto, Magda M. Santana, Thomas S. van Solinge, Shadi Mahjoum, Xandra O. Breakefield, Koen Breyne, Luís Pereira de Almeida
Journal: Molecular Therapy (2023)

In the central nervous system (CNS), the crosstalk between neural cells is mediated by extracellular mechanisms, including brain-derived extracellular vesicles (bdEVs). To study endogenous communication across the brain and periphery, we explored Cre-mediated DNA recombination to permanently record the functional uptake of bdEVs cargo over time. To elucidate functional cargo transfer within the brain at physiological levels, we promoted the continuous secretion of physiological levels of neural bdEVs containing Cre mRNA from a localized region in the brain by in situ lentiviral transduction of the striatum of Flox-tdTomato Ai9 mice reporter of Cre activity. Our approach efficiently detected in vivo transfer of functional events mediated by physiological levels of endogenous bdEVs throughout the brain. Remarkably, a spatial gradient of persistent tdTomato expression was observed along the whole brain, exhibiting an increment of more than 10-fold over 4 months. Moreover, bdEVs containing Cre mRNA were detected in the bloodstream and extracted from brain tissue to further confirm their functional delivery of Cre mRNA in a novel and highly sensitive Nanoluc reporter system. Overall, we report a sensitive method to track bdEV transfer at physiological levels, which will shed light on the role of bdEVs in neural communication within the brain and beyond. In the central nervous system (CNS), the crosstalk between neural cells is mediated by extracellular mechanisms, including brain-derived extracellular vesicles (bdEVs). To study endogenous communication across the brain and periphery, we explored Cre-mediated DNA recombination to permanently record the functional uptake of bdEVs cargo over time. To elucidate functional cargo transfer within the brain at physiological levels, we promoted the continuous secretion of physiological levels of neural bdEVs containing Cre mRNA from a localized region in the brain by in situ lentiviral transduction of the striatum of Flox-tdTomato Ai9 mice reporter of Cre activity. Our approach efficiently detected in vivo transfer of functional events mediated by physiological levels of endogenous bdEVs throughout the brain. Remarkably, a spatial gradient of persistent tdTomato expression was observed along the whole brain, exhibiting an increment of more than 10-fold over 4 months. Moreover, bdEVs containing Cre mRNA were detected in the bloodstream and extracted from brain tissue to further confirm their functional delivery of Cre mRNA in a novel and highly sensitive Nanoluc reporter system. Overall, we report a sensitive method to track bdEV transfer at physiological levels, which will shed light on the role of bdEVs in neural communication within the brain and beyond.
Trait-based approaches to predicting biological control success: challenges and prospects
Authors: Michal Segoli, Paul K. Abram, Jacintha Ellers, Gili Greenbaum, Ian C.W. Hardy, George E. Heimpel, Tamar Keasar, Paul J. Ode, Asaf Sadeh, Eric Wajnberg
Journal: Trends in Ecology & Evolution (2023)